The binding of ligands to cell surface receptors can stimulate specific enzymatic activities in the cell. In certain cases, the `signal` is transduced directly by the receptor which becomes capable of carrying out certain enzymatic functions. In other cases, the receptor triggers other proteins to carry out such enzymatic functions. The proteins which are modified by such activity are known as signal transduction proteins. Enzymatic activity stimulated includes tyrosine kinase (Pawson, Nature 373:573, 1995) and arginine methylase activity (Gary and Clarke, 1998, Prog Nucleic Acid Res. Mol. Biol. 61:65). It is known that many growth factor receptors and soluble tyrosine kinases are oncogenes and can transform cells. Thus, substrates of tyrosine kinases or the presence of post-translation modifications, such as arginine methylation, in response to growth factor receptors can serve as an indication of whether or not a cell is cancerous.
Signal transduction molecules often contain proline motifs and phosphotyrosine residues that serve as specific binding sites for Src-homology-3 (SH3) and Src-homology-2 (SH2) domain containing proteins (Pawson, Nature 373:573, 1995). SH2 recognizes peptides bearing phosphotyrosine (pTyr), and SH3 recognizes sequences containing one or more proline residues.
Sam68 (Src substrate activated during mitosis of 68 kDa), previously called p62 (GAP associated protein of 62 kDa) (Wong et al. (1992) Cell 69:551) is a signal transduction protein. It associates with SH2 and SH3 binding domains, for example those contained in certain tyrosine kinases. It can also bind single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA).